The blood-brain barrier (BBB) consists of a continuous layer of capillary endothelial cells that are sealed together by intercellular tight junctions. This structure is thought to be important in controlling the composition of the brain's interstitial fluid by means of specialized transport processes. In order to function most efficiently in response to the brain's requirements it is likely that transport processes in brain capillary endothelial cells are under regulatory control by metabolic, neurogenic or hormonal factors. The goal of this research project is to define mechanisms by which BBB permeability is regulated. We propose to study transport of Na ion, K ion, Cl ion, water, glucose, neutral amino acids and proteins into freshly isolated brain capillaries or into brain capillary endothelial cells maintained in tissue culture. We will also study transendothelial transport of these solutes using a continuous monolayer of cultured endothelial cells with separate solutions bathing the two sides of the cells. Transendothelial resistances, potential differences, and rates of solute flux will be determined. With these model systems we will investigate the effects of hormones, neurotransmitters, and metabolic alterations on brain capillary endothelial cell permeability.